Issue Date: March 23, 2015
Meet Jacqueline K. Barton, 2015 Priestley Medalist
The view from Jacqueline K. Barton’s office at California Institute of Technology is modest, despite the fact that it once belonged to two-time Nobel Laureate Linus Pauling and still showcases his analytical balance. “I never thought I’d end up here,” Barton says. As a girl born in 1952, her early plans never involved becoming a chemistry professor at a place like Caltech.
Even though it wasn’t the plan, being a chemist is something at which Barton has excelled—so much so that this year she is receiving the highest honor of the American Chemical Society, the Priestley Medal, “for brilliant work on electron transport in DNA, for dedication to training young investigators, and for unwavering support of the chemistry enterprise.”
“She’s one heck of a creative scientist,” says Jonas C. Peters, a chemistry professor at Caltech. “She started a field that has captivated a huge amount of interest and that bridges inorganic chemistry, biochemistry, and physical chemistry.”
“She is so incredibly enthusiastic and energetic,” says Erik Holmlin, who worked with Barton for his Ph.D. and is now president and chief executive officer of BioNano Genomics. “But she is also scientifically rigorous. She has this combination of rigor and passion that really drives things forward and pushes back frontiers.”
Barton first started pushing back frontiers as a child growing up in New York City, where she attended Riverdale Country School. At the time, the school was gender segregated. In addition to learning academic basics, the girls studied art and music while the boys focused on advanced math and science. The only coed class was American history.
But one of Barton’s teachers saw that she was good at math and decided that she should take calculus. “It was a major thing,” Barton says. “She went to my parents, and then she and my parents went to the headmistress.” Barton’s teacher prevailed, and Barton recalls being driven in a red station wagon to get to and from class on the boys’ campus.
Barton’s father was a judge and her mother a homemaker, “so the whole math and science thing was not part of their toolbox,” Barton says. “But my parents were always proud of me.”
In 1970, she entered Barnard College, the women’s college affiliated with Columbia University. Barton thought she might major in math, but chemistry won out. “Chemistry allows you to combine the rigors of mathematics with a little bit of something that could make a difference in the world,” Barton says. Also, “I love the beautiful molecular structures.”
Barton enrolled at Columbia for graduate school, where she initially thought that she’d focus on physical chemistry. Then chemistry professor Stephen J. Lippard pitched a project to her that involved binding inorganic complexes to DNA such that they would intercalate between the base pairs. “I got excited about DNA in the context of using it as a one-dimensional lattice to load up small molecules,” says Barton, noting that the project also involved some interesting statistical mechanics.
“She was a very bright, very articulate, very kind person,” Lippard says. “She was clearly destined for a really great career.”
After earning a Ph.D., Barton spent a year as a postdoctoral researcher at Bell Laboratories, then in 1980 she returned to New York to join the chemistry faculty at Hunter College. “I wasn’t ambitious,” Barton says. “When I was at Riverdale, I thought I’d be a high school teacher, then I thought I’d be a college teacher. I just sort of went from step to step.”
At Hunter, Barton started her research program by investigating DNA-binding metal complexes as analogs for restriction enzymes and other proteins that require metal ions to function. She also learned how to teach, write grants, and interact with her colleagues.
After a couple of years at Hunter, however, Barton felt constrained. She couldn’t do research at the level she wanted, she says, because of the teaching requirements and the graduate student pool. In 1983, Lippard moved to Massachusetts Institute of Technology and Barton replaced him on the Columbia faculty.
“She was really quite sensational,” says Ronald Breslow, one of Barton’s Columbia colleagues. “She’s a brilliant person generally, and she has huge amounts of energy and lots of enthusiasm. She’s everything you’re looking for in a colleague.
“She has a winning personality,” Breslow continues. “You can’t say that of all scientists—some succeed despite their personalities—but Jackie has a wonderful, warm personality and tremendous curiosity.”
At Columbia, Barton continued to work on DNA-binding complexes, exploring their enantioselectivity and sequence specificity. She developed a particularly close relationship with colleague Nicholas J. Turro, who died in 2012. “Nick looked out for me,” she says. He helped her figure out how to run a growing group and optimize her grant funds.
Turro and Barton also collaborated scientifically, using Turro’s expertise in photochemistry to probe Barton’s DNA complexes. That work led to a major finding by a joint postdoc, C. Vijay Kumar: DNA could transfer electrons between polypyridyl ruthenium and cobalt complexes (J. Am. Chem. Soc. 1986, DOI: 10.1021/ja00280a047; Science 1988, DOI: 10.1126/science.3420416). When the structure of DNA was first solved, chemists had proposed that the stacked aromatic bases might be a good electron transport medium, but Kumar, Barton, and Turro provided the first evidence for it.
When Barton moved to Caltech in 1989, some members of her group continued to explore DNA’s conductive properties. In 1993, postdoc Catherine J. Murphy demonstrated that DNA facilitated electron transfer along a 15-base pair DNA duplex—a distance of 40 Å (Science 1993, DOI: 10.1126/science.7802858). In 1999, Megan E. Núñez extended that distance to 200 Å (Chem. Biol. 1999, DOI: 10.1016/s1074-5521(99)80005-2).
But the idea that DNA might behave as a molecular wire was controversial. There was a lot of back and forth in the literature and harsh questions at conferences. “She was given a tough time,” Lippard says.
Barton prefers not to talk about it. “It was painful,” she concedes. “And it was very tough on my students.”
Barton approached the criticism head-on with more experiments, carefully controlled. In particular, she insisted that her group members work with DNA under conditions normally found in a cell—in water at room temperature. They also always used well-characterized DNA so they knew how the base pairs stacked and how strongly electron donor and acceptor complexes coupled to the helices.
After many years, “the bottom line is that we and others have learned that charge transfer through DNA can occur over long molecular distances. But it depends exquisitely on the stacking. Anything that screws up the stacking will screw up the electron transport,” Barton says. If a thymine-adenine step on the DNA ladder is switched to a cytosine-adenine or guanine-adenine mismatch, for example, electron transfer will stop. Theorists are still trying to work out the mechanisms at play.
Barton suggests that the debates were ultimately good for the field. In doing all the experiments to satisfy the critics, she says, “we learned a lot more than we would’ve learned otherwise.”
Alumni of her lab add that they also learned a few things about doing science.
“I can’t say I enjoyed it at the time—I think that we sent my first paper to 10 different journals before it was accepted,” says Shana Kelley, who got her Ph.D. from Caltech and is now a professor of pharmaceutical sciences at the University of Toronto. “But it taught me that you have to have a thick skin, you have to do the experiments to understand what’s going on, and you have to have the tenacity to stick with your ideas and not get discouraged.”
The fact that Barton’s group members were able to come through the controversy with something positive to say is a testament to Barton’s adept mentoring and ability to share her enthusiasm for science.
“As a mentor, she was fabulous,” says Murphy, who is now a chemistry professor at the University of Illinois, Urbana-Champaign. “She was always sure it was going to work and we were going to figure out a way no matter what.”
“She has this amazing energy that she passes on to anyone who talks with her,” says Valérie C. Pierre, who was a postdoc in Barton’s lab and is now a chemistry professor at the University of Minnesota, Twin Cities. “You would go into her office when nothing was working and come out encouraged to try the next experiment.”
Barton sets high expectations, Kelley notes. But at the same time, “she really watches her people closely to see what they excel at and help them to hone their skills,” Kelley says. “She taught me to be the very best scientist I could be.”
“The best part of what we do is help educate these young people and watch them turn into independent scientists,” Barton says. “When they defend their thesis, sitting there listening to them give their talk is just the most exciting thing in the world!”
But even when students decide that a scientific research career isn’t for them, Barton remains supportive. After getting her Ph.D. from Caltech, Tashica Williams Amirgholizadeh went to law school and is now corporate counsel at Gilead Sciences. Barton “recognizes and appreciates that not everyone wants to follow the same path,” Amirgholizadeh says.
In addition to taking on scientific challenges and mentoring group members, Barton has contributed to the chemistry enterprise globally as a member of the Dow Chemical Board of Directors, which she joined in 1993. Many board members are not scientists, and “the board looks to her for third-party validation on things they’re hearing from management,” says Andrew N. Liveris, Dow’s CEO. Barton helps explain Dow’s science to other board members—things such as why phosgene is a valuable synthetic building block—even as she pushes Dow management to ensure that the company is doing the best it can technologically.
“What I hope and have to bring to the board is some calibration of how good Dow’s R&D operation is and where we stand on environment, health, and safety issues,” Barton says.
Or as Liveris puts it, she helps the company with both offense and defense. “I have deep admiration for her as a scientist, leader, and terrific person,” he adds.
Barton is also currently serving in her second consecutive term as chair of the Caltech Division of Chemistry & Chemical Engineering. Caltech’s academic administration is lean, she notes—there are only six division chairs, the provost, and the president—so division chairs have a great deal of influence.
“Her strengths are her focus on critical problems and her energy in working on them—she doesn’t drop the ball,” colleague Harry B. Gray says. “Sometimes she has to make tough decisions that may be unpopular in some cases, but she goes ahead.”
Barton’s priorities have been fund-raising and hiring. Fund-raising has gone well—so far, Barton has raised $20 million to fund graduate fellowships.
As for hiring, Caltech has several chemistry faculty nearing retirement, and the push is on to ensure that the division’s future is as bright as its past. As part of that, Barton has created a diversity committee to try to figure out how the division can improve its recruiting. “The two-body problem continues to be difficult,” Barton says. But “I think the administration is increasingly committed to coming up with creative solutions,” she adds.
Barton’s colleagues note that she is just as good about mentoring young faculty as she is her group members. She helps foster a supportive atmosphere that gives junior faculty confidence, says Caltech chemistry professor Sarah E. Reisman.
Barton has contributed to the chemistry enterprise through other service, although she’s cautious and strategic about what she takes on. “You can only have so many things on your plate,” she says.
She manages her commitments by delegating. “I love to hire people who are smart and competent and that I can trust,” Barton says. Her group members have their responsibilities. Maureen S. Renta, her assistant of 25 years, “does everything for the group that doesn’t have to do with science,” Barton says. Amy Woodall-Ojeda and other division staff handle whatever else doesn’t require Barton’s direct attention. And Barton’s longtime nanny-housekeeper, Natividad Loeza, keeps things running at home.
These days, Barton’s group continues to work in three areas. One is determining whether cells use DNA-facilitated electron transfer as a means to monitor DNA integrity. Another is exploiting DNA electrochemistry for diagnostic applications, such as distinguishing tumors from normal tissue by looking for highly methylated DNA. The third is designing metal complexes that bind at DNA base pair mismatches for possible cancer treatments. Although Barton’s group is smaller than it used to be—part of that is her chair responsibilities, part is the overall funding climate—she seems no less enthusiastic about her science. “It’s fun!” she emphasizes.
“People who work for Jackie see a brilliant scientist who is strategic and tough,” says Madeleine Jacobs, former ACS executive director and CEO. The combination of that, Jacobs says, with Barton’s compassion and generosity make her a truly exceptional role model.
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